Pharmaceuticals and Medical Devices Safety Information No. 226 July 2006
Table of Contents
1. Effects on implantable medical devices (cardiac pacemakers and cardioverter defibrillators) by new system mobile phone terminals ········································································································ 3
2. Important Safety Information ·································································· 5 .1. Atorvastatin Calcium Hydrate ··························································· 5 .2. Goshajinkigan ·················································································· 9
3. Revision of PRECAUTIONS (No. 177) Chlorpromazine Hydrochloride/Promethazine Hydrochloride/Phenobarbital (and 8 others) ································································································ 12
4. List of products subject to Early Post-marketing Phase Vigilance ································································································· 16
This Pharmaceuticals and Medical Devices Safety Information (PMDSI) is issued based on safety information collected by the Ministry of Health, Labour and Welfare. It is intended to facilitate safer use of pharmaceuticals and medical devices by healthcare providers. PMDSI is available on the Pharmaceuticals and Medical Devices Agency website (http://www.pmda.go.jp/english/index.html) and on the MHLW website (http://www.mhlw.go.jp/, Japanese only).
Published by Translated by
Pharmaceutical and Food Safety Bureau, Pharmaceuticals and Medical Devices Agency Ministry of Health, Labour and Welfare
Pharmaceutical and Food Safety Bureau, Office of Safety, Ministry of Health, Labour and Welfare Pharmaceuticals and Medical Devices Agency 1-2-2 Kasumigaseki, Chiyoda-ku, Tokyo 3-3-2 Kasumigaseki, Chiyoda-ku, Tokyo 100-8916 Japan 100-0013 Japan E-mail: [email protected]
This translation of the original Japanese text is for information purpose only (in the event of inconsistency, the Japanese text shall prevail).
Pharmaceuticals and Medical Devices Safety Information No. 226 July 2006 Pharmaceutical and Food Safety Bureau, Ministry of Health, Labour and Welfare, Japan
[Outline of Information]
No. Subject Measures Outline of information Page Since the results of “Studies Relating to The Effects of Electromagnetic Waves on Medical Devices (Confirmation of Effects of Electromagnetic Waves Effects on implantable medical from Mobile Phone Terminals of the 800 MHz Band devices (cardiac pacemakers W-CDMA System on Implantable Medical 1 and cardioverter defibrillators) Devices)” conducted by Ministry of Internal Affairs 3 by new system mobile phone and Communications (MIC) in FY2005 were terminals publicized on May 30 of this year, the contents of this study will be introduced here, in addition to promoting awareness among healthcare providers, etc. once more. Presents contents of revisions, reference materials, and a case summary that served as the basis for these revisions to important adverse reactions included Atorvastatin Calcium Hydrate P under the PRECAUTIONS section of package 2 5 (and 1 other) C inserts of drugs that have been revised in accordance with the Notification after the previous bulletin (Pharmaceuticals and Medical Devices Safety Information No. 225). Chlorpromazine Hydrochloride/Promethazine 3 Hydrochloride/Phenobarbital Revision of PRECAUTIONS (No. 177) 12 (and 8 others) Products subject to Early Lists products subject to the Early Post-marketing 4 Post-marketing Phase 16 Vigilance Phase Vigilance as of July 1, 2006. D: Distribution of Dear Healthcare Professional Letters P: Revision of PRECAUTIONS C: Case Reports
Reporting of safety information such as adverse reactions to the Minister of Health, Labour and Welfare is a duty of medical and pharmaceutical providers.
If medical and pharmaceutical providers such as physicians, dentists, and pharmacists detect adverse reactions, infections associated with drugs or medical devices, or medical device adverse events, they are obligated to report them to the Minister of Health, Labour and Welfare directly or through the marketing authorisation holder. As medical and pharmaceutical providers, drug retailers with a second-class license and household distributors are also required to report safety issues related to drugs and medical devices.
1
Effects on implantable medical devices (cardiac pacemakers and cardioverter defibrillators) by new system mobile phone terminals
With regard to effects on implantable cardiac pacemakers and implantable cardioverter defibrillators (ICDs) (hereinafter referred to as “implantable medical devices”) by mobile phone terminals etc., awareness was promoted in Pharmaceuticals and Medical Devices Safety Information No. 136 (March 1996 edition), No. 137 (May 1996 edition), No. 143 (June 1997 edition), No. 155 (June 1999 edition), No. 173 (January 2002 edition), No. 179 (July 2002 edition), No. 190 (June 2003 edition), No. 203 (July 2004 edition), and No. 216 (August 2005 edition). Ministry of Internal Affairs and Communications (MIC) has been implementing studies relating to the effects of electromagnetic waves on medical devices since FY2000. In FY2005, “Guidelines for Preventing the Effects of Electromagnetic Waves From Various Types of Equipment on Implantable Medical Equipment” (established August 2005, hereinafter referred to as “Guidelines”) was established based on the results of past studies. Recently, MIC conducted a study on the effects on implantable medical devices from electromagnetic waves emitted from mobile phone terminals of a system that was newly implemented (800 MHz band W-CDMA system, hereinafter referred to as “new system mobile phone terminals”). As a result, it was publicized on May 30 of this year that it is appropriate to apply the current guidelines stating that “mobile phone terminals should be separated from the implant site of cardiac pacemakers by a distance of more than approximately 22 cm and more” even for mobile devices that were investigated in this study. In this issue, the contents of the study that was implemented by MIC recently are introduced. With regard to the results of this study by MIC and the revised Guidelines based on this survey, please refer to [http://www.soumu.go.jp/s-news/2006/060530_1.html] (in Japanese), as well.
1. Contents of the recent study conducted by MIC With regard to the effects of electromagnetic waves emitted from typical models of mobile phone terminals used in mobile telephone services of the 800 MHz band W-CDMA system recently put into practical use on typical models of implantable medical devices that are currently used, a study was conducted by establishing experimental conditions where these effects are thought to be the largest. (1) Mobile phone terminals With the cooperation of mobile telephone companies, a study was conducted on the following mobile phone terminal. • New system mobile phone terminal (800 MHz band W-CDMA system): 1 model (note) (note): For the mobile phone terminal subject to the study, a model with the highest radiation intensity of electromagnetic waves was selected from among the models that could be obtained while the study was being conducted. (2) Implantable medical devices With the cooperation of the Pacemaker Committee, a study was conducted on the following implantable medical devices. • Implantable cardiac pacemakers: 30 models • ICDs: 9 models
Pharmaceuticals and Medical Devices 3 July 2006 Safety Information No. 226 (3) Overview of study results With regard to implantable cardiac pacemakers, an effect to the pacing function(*1) was confirmed. This effect can be reduced and the pacemakers can be restored to their appropriate pacing functions if the mobile phone terminal is moved away. The distance at which this effect was confirmed when the mobile phone terminal was in a position the furthest away from the pacemakers (maximum interference distance) was 3 cm. With regard to ICDs, an effect on either the pacemaker function(*2) or defibrillation function(*3) could not be confirmed.
(Note): In this study, testing was performed under strict conditions, such as by setting the transmission output of the mobile phone terminal to the maximum, so that the effects on implantable medical devices would be the largest. Consequently, it is not appropriate to compare between the study condition (ex. including the largest distance away at which the effect was confirmed) and the normal condition, such as by setting to the regular transmission output of the mobile phone terminal.
2. Precautions regarding implantable medical devices Upon conducting this study, the maximum interference distance with regard to effects on implantable medical devices by new system mobile phone terminals was found to be 3 cm. At the same time, in the “Guidelines relating to the use of mobile phone terminals to prevent implantable medical devices from effects of electromagnetic waves” (*1), it is stipulated that mobile phone terminals should be “placed at least approximately 22 cm away” from the medical devices. Consequently, since it is considered that effects on implantable medical devices by mobile phone terminals can be prevented by continuing to adhere to “placed at least approximately 22 cm away” that is given in the current guidelines, it is request that patients continue to be instructed to adhere to the current guideline, and that family members, etc. also be instructed to do so if the patient is a child, etc.
*1: This translation was based on the description of PMDSI in Japanese.
Pharmaceuticals and Medical Devices 4 July 2006 Safety Information No. 226
2
Important Safety Information
This section presents contents of revisions, reference materials, and a case summary that served as the basis for these revisions to important adverse reactions included under the PRECAUTIONS section of package inserts of drugs that have been revised in accordance with the Notification after the previous bulletin (Pharmaceuticals and Medical Devices Safety Information No.225).
1 Atorvastatin Calcium Hydrate
Brand Name Lipitor Tablets 5 mg and 10 mg (Astellas Pharma Inc.) (name of company) Therapeutic Category Hyperlipidaemia agents Hypercholesterolaemia Indications Familial hypercholesterolaemia
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[Adverse Reactions Hepatitis fulminant, hepatitis, hepatic function disorder, jaundice: Patient (clinically significant should be carefully monitored through periodic testing etc. If abnormalities are adverse reactions)] observed, administration should be discontinued and appropriate measures should be taken.
Case Summary Patient Daily dose/ Adverse reactions No. Reason for use Treatment Remarks Sex/Age (complications) duration Clinical course and therapeutic measures 1 Female Hyperlipidaemia 10 mg Hepatitis fulminant Company 50s (reflux 77 days 3 days before administration: report oesophagitis, Low back pain developed. After 3 or 4 times of ovarian failure, oral administrations of OTC analgesic drugs, gastric ulcer, epigastralgia, queasy and vomiting developed. The insomnia, patient was drinking fluids, but vomited climacteric disturbance) immediately and did not intake any food at all. The patient seemed to have been taking OTC drugs (cold medicine) often, but details are unknown. History of blood transfusions: unknown.
Pharmaceuticals and Medical Devices 5 July 2006 Safety Information No. 226
1 day before administration: Since the symptoms persisted, the patient made an outpatient visit to hospital A. She was hospitalized after undergoing drip infusion. The patient was diagnosed with reflux oesophagitis, gastric ulcer, insomnia, hyperlipidaemia, and climacteric disturbance, and was prescribed oral medicines. On day 1 of administration: Administration of this drug, lansoprazole, zolpidem tartrate, quazepam, mosapride citrate, and domperidone was initiated. On day 2 of administration: Administration of conjugated estrogens and medroxyprogesterone acetate was initiated. On day 4 of administration: Symptoms for reflux oesophagitis (queasy) improved. The patient was discharged from the hospital. On day 22 of administration: Administration of mosapride citrate and domperidone was discontinued. On day 64 of administration: Administration of zolpidem tartrate and quazepam was discontinued. On day 75 of administration: The patient laid her work aside and went home due to physical deconditioning. On day 77 of administration (day of discontinuation): Administration of this drug and lansoprazole discontinued. 3 days after discontinuation: The patient was sleeping or eating, and continued vomiting. Administration of conjugated estrogens and medroxyprogesterone acetate was discontinued. 4 days after discontinuation: Around noon, the patient was emergently sent to hospital A due to loss of consciousness since the morning. Due to advanced liver disorder and consciousness disturbed (hepatic encephalopathy: stage IV, JCS: 300), the patient was sent to emergency center of hospital B. Immediately after transportation, the patient was fitted with tracheal intubation and respirator. Since she also had renal disorder, CHDF (continuous hemodiafiltration) was initiated. Administration of fresh frozen human plasma and plasma exchange were initiated. Afterwards, hypothermia (unmeasurable) developed, and blood pressure was 88/48 mmHg, pulse was 86 pulses/minute, JCS was 30 to 100, jaundice was () and coloring yellow was (). Hypoglycaemic with a blood sugar of 38 mg/dL was also indicated, and diagnosed as having hepatic encephalopathy of stage III and diagnosed with hepatitis fulminant. In the nighttime, plasma exchange (40 units of fresh frozen human plasma) was performed. Afterwards, CHDF (300 mL/h of dialysate, 700 mL/h of fluid replacement and 1000 mL/h of physiological saline) was initiated as artificial hepatic assist treatment.
Pharmaceuticals and Medical Devices 6 July 2006 Safety Information No. 226 Methylprednisolone sodium succinate at 1 g/day was administered as immunosuppressive treatment. No abnormalities were found in chest/abdominal X rays. Based on abdominal CT, intrahepatic ductal dilatation was (), dilatation of the common bile duct was (), ascites were () and there was atrophy in the hepatic left lobe. Based on an echo, the surface of the liver was smooth, marginal dull, intrahepatic mass was (), and ascites were (). 5 days after discontinuation: In the morning, hepatic encephalopathy was worsened to stage V. Although they attempted to perform a DLST, the lymphocyte count was low and could not be measured. Consideration was given to a liver transplant but was abandoned due to the decision that the patient would not be able to tolerate a transplant due to vitals being unfavorable. In the night, blood pressure was decreased to the 60 mmHg range. 6 days after discontinuation: Blood pressure and pulse continued to decrease. The patient died before dawn. Hepatic necropsy: Necrosis of band-like necrosis hepatocellular in area around central venous was confirmed. It was accompanied by haemorrhage. Small amount of eosinophils and infiltration of neutrophil are confirmed in portal region, but significant lymphocytic infiltration and cholangiole reactions were obscure. Though inflammatory reactions were scarce, necrosis of necrosis hepatocellular was conspicuous, and eosinophilic infiltration was confirmed. (cause of death: hepatitis fulminant) Concomitant medications: zolpidem tartrate, lansoprazole, medroxyprogesterone acetate, conjugated estrogens, quazepam, mosapride citrate, domperidone
Clinical Laboratory Values On day 1 of administration 4 days after discontinuation 5 days after discontinuation AST (GOT) (IU/L) 19 4950 5005 ALT (GPT) (IU/L) 13 1935 1469 Al-P (IU/L) 401 566 422 -GTP (IU/L) 80 409 263 LDH (IU/L) 192 5971 7926 Total bilirubin (mg/dL) 0.4 2.5 3.9 Prothrombin activity (%) -- 30.0 51.1 Blood ammonia (g/dL) -- 687 234 HAV (), HBV (), HCV (), CMV (), EBV infected, antinuclear antibody () AST: Asparate Aminotransferase -GTP: -Glutamyltranspeptidase ALT: Alanine Aminotransferase LDH: Lactate Dehydrogenase Al-P: Alkaline Phosphatase
Pharmaceuticals and Medical Devices 7 July 2006 Safety Information No. 226
Patient Daily dose/ Adverse reactions No. Sex/ Reason for use Treatment Remarks Age (complications) duration Clinical course and therapeutic measures 2 Female Hypercholesterolaemia 5 mg Drug-induced hepatitis Company 50s (essential 55 days 2 days before administration: report hypertension, The patient complained of non-rotatory vertigo from angina pectoris, early morning 2 days before, and made a hospital visit. and suspected Blood pressure was 180/100 mmHg. Findings of a diabetes decrease in ST were confirmed in an electrocardiogram. mellitus) Heart rate was 95 beats/minute, total cholesterol was 242 mg/dL in blood test. Triglyceride was 120 mg/dL and HDL-cholesterol was 60 mg/dL. Glucose (2) was confirmed in urine analysis. On day 1 of administration: Administration of this drug, valsartan, trapidil, and kallidinogenase was initiated. On day 4 of administration: 75 g glucose tolerance test was performed. As a result, 87 mg/dL before tolerance, 167 mg/dL after 30 minutes, 135 mg/dL after 60 minutes, 115 mg/dL after 120 minutes. With regard to diabetes mellitus, only dietary instructions were given. On day 55 of administration (day of discontinuation): Abnormal value was confirmed in liver function test, administration of this drug, valsartan, trapidil, and kallidinogenase was discontinued. 1 day after discontinuation: Drip infusion of 500 mL of 5% glucose and 40 mL of glycyrrhizin/glycine/cysteine was initiated (for 10 days). 2 days after discontinuation: Based on negative hepatitis viral markers and normal antinuclear antibody, the patient was diagnosed with drug-induced hepatitis. 12 days after discontinuation: Intravenous injection of 40 mL of glycyrrhizin/glycine/cysteine was initiated (for 12 days). 22 days after discontinuation: The symptoms were improved. Concomitant medications: valsartan, trapidil, kallidinogenase
Clinical Laboratory Values On day 55 of administration 2 days after 5 days after 12 days after 17 days after 22 days after
(day of discontinuation discontinuation discontinuation discontinuation discontinuation discontinuation) AST (GOT) (IU/L) 1551 1049 379 81 48 38 ALT (GPT) (IU/L) 2560 2300 1200 268 103 52 Al-P (IU/L) 530 797 784 475 332 278 -GTP (IU/L) 244 270 519 362 255 199 LDH (IU/L) -- 950 394 273 259 253 Total bilirubin (mg/dL) 1.3 1.7 1.4 1.2 1.5 1.4 Hepatitis virus (), antinuclear antibody normal AST: Asparate Aminotransferase -GTP: -Glutamyltranspeptidase ALT: Alanine Aminotransferase LDH: Lactate Dehydrogenase Al-P: Alkaline Phosphatase
Pharmaceuticals and Medical Devices 8 July 2006 Safety Information No. 226
2 Goshajinkigan
Brand Name TSUMURA Goshajinkigan Extract Granules for Ethical Use (Tsumura & Co.) (name of company) Therapeutic Category Kampo medicines Following symptoms with decreased urine volume, polyuria, occasional dry mouth, fatiguability and feeling of cold in the extremities: Indications Leg pain, low back pain, numbness, blurred vision in old patients, pruritus, dysuria, frequent urination and oedema
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Pharmaceuticals and Medical Devices 9 July 2006 Safety Information No. 226 Case Summary Patient Daily dose/ Adverse reactions No. Reason for use Treatment Remarks Sex/ Age (complications) duration Clinical course and therapeutic measures 1 Female Pain in right knee 7.5 g Interstitial pneumonia Company 70s (hyperthyroidism, 119 days Approx. 16 years before administration: report interstitial Due to aortic stenosis, the patient was visiting this pneumonia, pain department regularly. in right knee) Approx. 3 years before administration: Pulmonary fibrosis was confirmed, but it was localized to part of the right lower lobe. On day 1 of administration: Administration of this drug was started for pain in right knee. On day 110 of administration: Body temperature was increased to 37.4°C, and dry cough and dyspnoea of HJ IV to V on exertion developed. On day 119 of administration (day of discontinuation): The patient received an outpatient consultation from this department. Since extensive ground-glass opacity had newly developed mainly around the right upper and lower lung fields, the patient underwent emergency hospitalization on the same day. Since atypical pneumonia could not be denied based on chest findings, CRP increased, slight fever etc., clarithromycin was administrated. Administration of this drug was discontinued and observing clinical course, the symptoms improved with rest. 42 days after discontinuation: The patient was discharged from the hospital. She was undergoing monitoring of clinical course as an outpatient. 50 days after discontinuation: Worsening of symptoms was not confirmed. Concomitant medications: thiamazole, diltiazem hydrochloride, etizolam
Clinical Laboratory Values On day 119 of Before On day 55 of 29 days after 50 days after administration administration administration discontinuation discontinuation (day of discontinuation) WBC (/mm3) 4100 4000 5800 4400 4700 Eosinophils (%) 0.3 0.2 8.0 2.4 0.7 LDH (IU/L) 193 209 243 208 -- WBC: White Blood Cell LDH: Lactate Dehydrogenase
Blood gases On day 119 of 9 days after 29 days after administration discontinuation discontinuation (day of discontinuation) pH 7.432 7.436 7.405
PaO2 (torr) 70.1 69.2 84.6
PaCO2 (torr) 37.9 38.2 40.1
PaO2: Partial Pressure Arterial Oxygen PaCO2: Partial Pressure of Carbon Dioxide in Artery
Pharmaceuticals and Medical Devices 10 July 2006 Safety Information No. 226 Immune serum test DLST (S.I.) On day 119 of 1 day after 10 days after administration discontinuation discontinuation (day of discontinuation) RA test Negative -- This drug 523% Antinuclear antibody -- Positive Complement CH50 -- 49
Pharmaceuticals and Medical Devices 11 July 2006 Safety Information No. 226
3
Revision of PRECAUTIONS (No. 177)
This section presents details of revisions to the PRECAUTIONS section of package inserts and brand names of drugs that have been revised according to the Notifications after the previous bulletin (Pharmaceuticals and Medical Devices Safety Information No.225) (excluding those presented in “2. Important Safety Information” of this Bulletin), together with reference materials.
[Brand Name] Vegetamin Tablets-A, Vegetamin Tablets-B (Shionogi & Co., Ltd.)
[Contraindications] Infants under 2 years of age
[Use in Children] This drug should not be used in infants under 2 years of age. [It has been reported that in foreign countries, administration of promethazine drugs to infants under 2 years of age has resulted in life-threatening respiratory depression.]
[Brand Name] Paxil Tablets 10 mg and 20 mg (GlaxoSmithKline K.K.)
[Important Precautions] Since it has been reported that young adults, especially those with major depressive disorder (MDD), may be at increased risk for suicidal behaviour (completed suicide and suicide attempt) during treatment with this drug.careful monitoring should be given in such patients.
[Other Precautions] As a results of an analysis of the placebo-controlled clinical trials of this drug in adult patients with psychiatric disorders conducted overseas, although the study showed a higher frequency of suicidal behaviour(completed suicide and suicide attempt) in patients aged 18-24 years) treated with this drug compared with placebo (17/776 [2.19%] versus 5/542 [0.92%]), although this difference was not statistically significant. In patients with MDD, there was a statistically significant increase in the frequency of suicidal attempts in patients treated with this drug compared with placebo (11/3455 [0.32%] versus 1/1978 [0.05%]; all of the events were suicide attempts). The majority of these attempts for this drug were in patients aged 18-30 years..
Pharmaceuticals and Medical Devices 12 July 2006 Safety Information No. 226
[Brand Name] Atarax, Atarax Tablets 25 mg, Atarax-P Parenteral Solution (Pfizer Japan Inc.) and others Atarax-P Powder 10%, Atarax-P, Atarax-P Syrup, Atarax-P Dry Syrup (Pfizer Japan Inc.) and others
[Contraindications] Patients with a history of hypersensitivity to ingredients of this drug, cetirizine, piperazine derivative, aminophylline, or ethylenediamine Patients with porphyria Pregnant women or women who may be pregnant
[Use in Pregnant, This drug should not be used in pregnant women or women who may be pregnant Parturient and Nursing [It has been reported that upon administering this drug to women in the early stage Women] of pregnancy (approximately 3 months), the women gave birth to babies with birth defects such as cleft palates. In addition, it has also been reported that due to administration of this drug during pregnancy, psychoneurotic symptoms such as somnolence neonatal, hypotonia neonatal, withdrawal symptoms, extrapyramidal disorder, clonic movements, and central nervous system depression, and neonatal hypoxia were observed in neonates.] This drug should not be administered to nursing mothers. [Although excretion of this drug in breast milk has not been established, it has been reported that central nervous system depression and hypotonicity have developed in neonates while nursing.]
4
[Brand Name] PL Granules, PL Granules for Children (Shionogi & Co., Ltd.) and others
[Contraindications] Infants under 2 years of age
[Use in Children] This drug should not be used in infants under 2 years of age. [It has been reported that in foreign countries, administration of promethazine drugs to infants under 2 years of age has resulted in life-threatening respiratory depression.]
[Brand Name] Xalatan Eye Drops (Pfizer Japan Inc.)
[Important Precautions] Temporary vision blurred may occur after ocular instillation of this drug. Patients should be advised to refrain from engaging in operating machines or driving a car etc. until symptoms recover.
Pharmaceuticals and Medical Devices 13 July 2006 Safety Information No. 226
[Brand Name] Diovan Tablets 20 mg, 40 mg, 80 mg, and 160 mg (Novartis Pharma K.K.)
[Adverse Reactions Agranulocytosis, white blood cell decreased, platelets decreased: (clinically significant Agranulocytosis, white blood cell decreased, and platelets decreased may occur. adverse reactions)] Patient should be carefully monitored and if any abnormalities are observed, appropriate measures should be immediately taken.
7
[Brand Name] Hiberna Sugar-coated Tablets 5 mg and 25 mg, Hiberna Injection (Mitsubishi Pharma Corporation), Pyrethia Tablets (Shionogi & Co., Ltd.) and others Hiberna Powder 10% (Mitsubishi Pharma Corporation) Pyrethia Fine Granules (Shionogi & Co., Ltd.)
[Contraindications] Infants under 2 years of age
[Use in Children] This drug should not be used in infants under 2 years of age. [It has been reported that in foreign countries, administration to infants under 2 years of age has resulted in life-threatening respiratory depression.]
[Brand Name] Immunobladder Intravesical 40 mg and 80 mg (Japan BCG Laboratory)
[Adverse Reactions BCG infection: This drug is a live bacterial preparation, and may cause (clinically significant disseminated BCG infection, local BCG infection and ectopic BCG infection. In adverse reactions)] addition, sepsis, hepatitis, cerebrospinal meningitis, cystitis, pyelonephritis, nephritis, prostatitis, epididymitis, aneurysm, etc. may occur. Discontinue administration and take appropriate measures in such cases, and conduct combination therapy with chemotherapeutics-tuberculosis preparations such as isoniazid, rifampicin and ethambutol. BCG is not susceptible to pyrazinamide. Disseminated BCG infection: In clinical trials of this drug, cases of death thought to be resulting from disseminated BCG infections associated with administration of BCG after traumatic injury from catheter insertion etc. were confirmed. Disseminated BCG infection is suggested by influenza-like febrile symptoms that persist for 48 hours and more, pyrexia of 39°C and higher, generalized symptoms that grow intense from repeated dose, or continuation of liver function test abnormalities. Local BCG infection: Continued BCG infection in the ureter, renal pelvis, kidney, prostate, epididymis, etc. of the bladder and lumen where this drug was locally administered has been reported. Ectopic BCG infection: Ectopic BCG infection in aneurysms etc. has been reported. Renal failure: Serious renal disorders such as renal failure etc. may occur. Patients should be carefully monitored and if any abnormalities are observed, appropriate measures, such as discontinuing treatment should be taken.
Pharmaceuticals and Medical Devices 14 July 2006 Safety Information No. 226
Over the counter drugs 9 Goshajinkigan
[Brand Name] Kanebo Goshajinkigan Extract Tablets (Kanebo, Ltd.) and others
[Consultation] In case of the following, immediately discontinue administration and bring this document to your doctor or pharmacist for consultation. If the following symptoms are observed after taking this drug In rare instances, the following serious symptoms may occur. Visit a physician immediately in such cases. Interstitial pneumonia: Shortness of breath, dyspnoea, and pyrexia accompanying cough may occur.
Pharmaceuticals and Medical Devices 15 July 2006 Safety Information No. 226
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List of products subject to Early Post-marketing Phase Vigilance
(As of July1, 2006) Nonproprietary name Name of the marketing Date of EPPV Brand name authorisation holder initiation Miglitol Sanwa Kagaku Kenkyusho Co., January 11, 2006 Seibule Tab. 25 mg, 50 mg, and 75 mg Ltd. Potassium Clavulanate/Amoxicillin GlaxoSmithKline K.K. January 17, 2006 Clavamox Dry Syrup for Pediatric Paroxetine Hydrochloride Hydrate GlaxoSmithKline K.K. January 23, 2006 Paxil Tablets 10 mg and 20 mg*1 Ciclosporin Santen Pharmaceutical Co., Ltd. January 23, 2006 Papilock Mini Ophthalmic Solution 0.1% Placental Gonadotrophin Serono Japan Co., Ltd. January 30, 2006 Profasi Injection 5000*2 Zanamivir Hydrate GlaxoSmithKline K.K. February 17, 2006 Relenza*3 Baclofen Daiichi Pharmaceutical Co., Ltd. April 1, 2006 Intrathecal Gabalon 0.005%, 0.05%, and 0.2% Interferon Beta Toray Industries, Inc. April 20, 2006 Feron*4 Epoetin Beta (Genetical recombination) Epogin Injection Ampoule 750, 1500, and 3000, Epogin Chugai Pharmaceutical Co., Ltd. April 20, 2006 Injection Syringe 750, 1500, and 3000*5 Somatropin (Genetical recombination) Eli Lilly Japan K.K. April 20, 2006 Humatrope C 6 mg and 12 mg*6 Zoledronic Acid Hydrate Novartis Pharma K.K. April 20, 2006 Zometa Injection 4 mg*7 Micafungin Sodium Astellas Pharma Inc. April 20, 2006 Funguard 50 mg and 75 mg for Infusion*8 Linezolid Pfizer Japan Inc. April 20, 2006 Zyvox Tablets 600 mg, Zyvox Injection 600 mg*9 Tosufloxacin Tosilate Nidek Co., Ltd. April 28, 2006 Tosuflo Ophthalmic Solution 0.3% Clopidogrel Sulfate Sanofi-Aventis K.K. May 8, 2006 Plavix Tablets 25 mg and 75 mg Silodosin Kissei Pharmaceutical Co., Ltd. May 11, 2006 Urief Cap. 2 mg and 4 mg Tosufloxacin Tosilate Toyama Chemical Co., Ltd. May 11, 2006 Ozex Ophthalmic Solution 0.3% Follitropin Alfa (Genetical recombination) Serono Japan Co., Ltd. May 11, 2006 Gonalef for S.C. Injection 75 and 150
Pharmaceuticals and Medical Devices 16 July 2006 Safety Information No. 226 Letrozole Novartis Pharma K.K. May 11, 2006 Femara Tablets 2.5 mg Loxoprofen Sodium Lead Chemical Co., Ltd. May 23, 2006 Loxonin PAP 100 mg Aripiprazole Otsuka Pharmaceutical Co., Ltd. June 8, 2006 Abilify Tablets 3 mg and 6 mg, Abilify Powder 1% Solifenacin Succinate Astellas Pharma Inc. June 8, 2006 Vesicare Tablets 2.5 mg and 5 mg Tolterodine Tartrate Pfizer Japan Inc. June 8, 2006 Detrusitol Capsules 2 mg and 4 mg Amphotericin B Dainippon Sumitomo Pharma June 20, 2006 AmBisome for Intravenous Infusion 50 mg Co., Ltd. Magnesium Sulfate/Glucose TOA Pharmaceuticals Co., Ltd. June 20, 2006 Magsent Injection 100 mL Note) Subject to additional indication etc. *1: An additional indication for “obsessive-compulsive disorder” *2: An additional indication for “induction of spermatogenesis in hypogonadotropic male hypogonadism” *3: An additional administration for “pediatrics” *4: An additional indication for “the improvement of viremia in compensated cirrhosis type C (except in the patients with HCV serogroup 1 and high blood HCV-RNA level)” *5: An additional indication for “anemia of prematurity” *6: An additional indication for “adult growth hormone hyposecretion (severe cases only)” *7: An additional indication for “bone lesions due to multiple myeloma and solid tumor metastases to bone” *8: An additional administration for “pediatrics” *9: Additional indications for “
Pharmaceuticals and Medical Devices 17 July 2006 Safety Information No. 226